Abstract
Amyloids are protein polymers that were initially linked to human diseases. Across the whole Tree of Life, many disease-unrelated proteins are now emerging for which amyloids represent distinct functional states. Most bacterial amyloids described are extracellular, contributing to biofilm formation. However, only a few have been found in the bacterial cytosol. This paper reviews from the perspective of synthetic biology (SynBio) our understanding of the subtle line that separates functional from pathogenic and transmissible amyloids (prions). In particular, it is focused on RepA-WH1, a functional albeit unconventional natural amyloidogenic protein domain that participates in controlling DNA replication of bacterial plasmids. SynBio approaches, including protein engineering and the design of allosteric effectors such as diverse ligands and an optogenetic module, have enabled the generation in RepA-WH1 of an intracellular cytotoxic prion-like agent in bacteria. The synthetic RepA-WH1 prion has the potential to develop into novel antimicrobials.
Highlights
Amyloids are protein polymers that were initially linked to human diseases
The mammalian prion protein (PrP) is a particular type of amyloid that can be “horizontally” transmitted between organisms as the causal infectious agent of spongiform encephalopathies, but recently this property has been attributed to the intraorganismic cell-to-cell transmission of many other amyloids involved in neurodegeneration, which are considered prion-like proteins
Functional amyloids and prion-like proteins have been described in bacteria
Summary
Amyloids are protein polymers that were initially linked to human diseases. Across the whole Tree of Life, many disease-unrelated proteins are emerging for which amyloids represent distinct functional states. BACTERIAL AMYLOIDS HAVE BOTH BRIGHT AND DARK SIDES Since the discovery of the amyloid nature of the curli (CsgA) protein fibers that form part of Escherichia coli biofilms [6], it has been found that analogous extracellular amyloids are built by other species in the Bacteria life domain (reviewed in references 7 and 8).
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